{"id":"W2807452056","doi":"10.1038/s41467-018-03234-8","title":"NAD+ analog reveals PARP-1 substrate-blocking mechanism and allosteric communication from catalytic center to DNA-binding domains","year":2018,"lang":"en","type":"article","venue":"Nature Communications","topic":"PARP inhibition in cancer therapy","field":"Medicine","cited_by":232,"is_retracted":false,"has_abstract":true,"ca_institutions":"Université de Montréal","funders":"Biological and Environmental Research; Basic Energy Sciences; Lawrence Berkeley National Laboratory; National Institute of General Medical Sciences; National Institutes of Health; National Cancer Institute; Canadian Institutes of Health Research; U.S. Department of Energy","keywords":"Allosteric regulation; NAD+ kinase; Poly ADP ribose polymerase; DNA; Chemistry; Biophysics; DNA repair; Nucleobase; DNA damage; DNA-binding domain; Biochemistry; Stereochemistry; Cell biology; Biology; Polymerase; Enzyme; Transcription factor; Gene","routes":{"ca_aff":true,"ca_fund":true,"ca_venue":false,"about_ca":false,"invisible_to_affiliation_only":false},"retraction":null,"screen":null,"direct_labels":[],"prediction":{"model_version":"codex-gemma-dda1882f352a","candidate_categories":[],"consensus_categories":[],"category_scores_codex":[0.0004062255,0.0002235444,0.0003331675,0.0002277099,0.0006239749,0.0001007637,0.0008345387,0.0003206804,0.00008344607],"category_scores_gemma":[0.0001365818,0.0002238958,0.00007332267,0.0005352946,0.0002462984,0.0002116071,0.0004619386,0.0008721715,0.0001121764],"about_ca_system_candidate":false,"about_ca_system_consensus":false,"about_ca_system_score_codex":0.0002630934,"about_ca_system_score_gemma":0.00007830185,"about_ca_topic_candidate":false,"about_ca_topic_consensus":false,"about_ca_topic_score_codex":0.0001275071,"about_ca_topic_score_gemma":0.001362067,"domain_scores_codex":[0.9984156,0.0002280326,0.00043525,0.0003553648,0.0002708881,0.000294804],"domain_scores_gemma":[0.9958867,0.0002906722,0.0001720456,0.003091934,0.0003245019,0.0002340817],"domain_codex":null,"domain_gemma":null,"domain_candidate":null,"domain_consensus":null,"study_design_codex":"bench_or_experimental","study_design_gemma":"not_applicable","study_design_scores_codex":[0.001068073,0.001751286,0.07637303,0.0001619772,0.001563052,0.00002967804,0.0210207,0.000005116271,0.7458135,0.1119085,0.03214693,0.008158184],"study_design_scores_gemma":[0.03369419,0.003119856,0.2957629,0.0101662,0.002471553,0.001160224,0.01138861,0.007989619,0.1697788,0.1040743,0.3546394,0.005754409],"study_design_candidate":"bench_or_experimental","study_design_consensus":null,"genre_codex":"empirical","genre_gemma":"empirical","genre_scores_codex":[0.9718245,0.002615457,0.0004678261,0.01667287,0.0002189328,0.0008195058,0.0001870842,0.0001680765,0.007025715],"genre_scores_gemma":[0.9792465,0.0009884791,0.01432441,0.004143257,0.0001567671,0.0001133049,0.0008559949,0.00004422675,0.0001270843],"genre_candidate":"empirical","genre_consensus":"empirical","teacher_disagreement_score":0.5760347,"threshold_uncertainty_score":0.9130207,"prediction_status":"machine_predicted_unvalidated"},"machine_scores":{"provisional":true,"baseline":true,"maturity_gate_passed":false,"score_opus":0.0359313609022584,"score_gpt":0.3426443673078713,"score_spread":0.3067130064056129,"validation_status":"score_only:v0-immature-baseline","note":"Baseline scores from an immature model (maturity gate not passed). Scores rank; they never assert a category."}}